SYSTEMATIC REVIEW
published: 09 June 2021
Edited by:
Maj Vinberg,
University Hospital of
Copenhagen, Denmark
Reviewed by:
Joel Paris,
McGill University, Canada
Steven Marwaha,
University of Birmingham,
United Kingdom
*Correspondence:
Benedikt Lorenz Amann
benedikt.amann@gmail.com
† These authors have contributed
equally to this work and share first
authorship
Specialty section:
This article was submitted to
Mood and Anxiety Disorders,
a section of the journal
Frontiers in Psychiatry
Received: 17 March 2021
Accepted: 14 May 2021
Published: 09 June 2021
Citation:
Massó Rodriguez A, Hogg B,
Gardoki-Souto I, Valiente-Gómez A,
Trabsa A, Mosquera D,
García-Estela A, Colom F, Pérez V,
Padberg F, Moreno-Alcázar A and
Amann BL (2021) Clinical Features,
Neuropsychology and Neuroimaging
in Bipolar and Borderline Personality
Disorder: A Systematic Review of
Cross-Diagnostic Studies.
Front. Psychiatry 12:681876.
doi: 10.3389/fpsyt.2021.681876
Frontiers in Psychiatry | www.frontiersin.org
doi: 10.3389/fpsyt.2021.681876
Clinical Features, Neuropsychology
and Neuroimaging in Bipolar and
Borderline Personality Disorder: A
Systematic Review of
Cross-Diagnostic Studies
Anna Massó Rodriguez 1,2† , Bridget Hogg 3,4,5† , Itxaso Gardoki-Souto 3,4,5 ,
Alicia Valiente-Gómez 1,3,4,6 , Amira Trabsa 1,3,5 , Dolores Mosquera 7 , Aitana García-Estela 4,6 ,
Francesc Colom 1,4,6,8 , Victor Pérez 1,4,6 , Frank Padberg 9 , Ana Moreno-Alcázar 3,4,6 and
Benedikt Lorenz Amann 1,3,4,6,10*
1
Institute of Neuropsychiatry and Addiction, Parc de Salut Mar, Barcelona, Spain, 2 Centro Salud Mental Infanto-Juvenil,
Parc de Salut Mar, Barcelona, Spain, 3 Centre Fòrum Research Unit, Institute of Neuropsychiatry and Addiction, Parc de
Salut Mar, Barcelona, Spain, 4 Mental Health Research Group, Hospital del Mar Medical Research Institute (IMIM), Barcelona,
Spain, 5 PhD Progamme, Department of Psychiatry and Forensic Medicine, Universitat Autònoma de Barcelona, Barcelona,
Spain, 6 Centro de Investigación Biomédica en Red de Salud Mental, Madrid, Spain, 7 Instituto de Investigación y Tratamiento
del Trauma y los Trastornos de la Personalidad (INTRA-TP) Center, A Coruña, Spain, 8 Departament of Basic, Evolutive and
Education Psychology, Universitat Autònoma de Barcelona, Barcelona, Spain, 9 Department of Psychiatry and
Psychotherapy, Klinikum der Universität München, Munich, Germany, 10 Department of Psychiatry and Forensic Medicine,
Universitat Autònoma de Barcelona, Barcelona, Spain
Background: Bipolar Disorder (BD) and Borderline Personality Disorder (BPD) have
clinically been evolving as separate disorders, though there is still debate on the
nosological valence of both conditions, their interaction in terms of co-morbidity or
disorder spectrum and their distinct pathophysiology.
Objective: The objective of this review is to summarize evidence regarding
clinical features, neuropsychological performance and neuroimaging findings from
cross-diagnostic studies comparing BD and BPD, to further caracterize their
complex interplay.
Methods: Using PubMed, PsycINFO and TripDataBase, we conducted a systematic
literature search based on PRISMA guidelines of studies published from January 1980
to September 2019 which directly compared BD and BPD.
Results: A total of 28 studies comparing BD and BPD were included: 19 compared
clinical features, 6 neuropsychological performance and three neuroimaging
abnormalities. Depressive symptoms have an earlier onset in BPD than BD. BD
patients present more mixed or manic symptoms, with BD-I differing from BPD
in manic phases. BPD patients show more negative attitudes toward others
and self, more conflictive interpersonal relationships, and more maladaptive
regulation strategies in affective instability with separate pathways. Impulsivity
seems more a trait in BPD rather than a state as in BD. Otherwise, BD and
BPD overlap in depressive and anxious symptoms, dysphoria, various abnormal
temperamental traits, suicidal ideation, and childhood trauma. Both disorders
differ and share deficits in neuropsychological and neuroimaging findings.
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Massó Rodriguez et al. Borderline Personality Disorder Bipolar Disorder

Conclusion: Clinical data provide evidence of overlapping features in both disorders,

with most of those shared symptoms being more persistent and intense in BPD.
Thus, categorical classifications should be compared to dimensional approaches in
transdiagnostic studies investigating BPD features in BD regarding their respective
explanatory power for individual trajectories.
Systematic Review Registration: The search strategy was pre-registered in
PROSPERO: CRD42018100268.
Keywords: bipolar disorder, borderline personality disorder, clinical features, cognitive functions, neuroimaging,
affective continuum

INTRODUCTION Medicine (Medical Subject Heading Terms, MeSH) and the

A recent meta-analysis of 42 studies (1) found that 21.6%
of patients suffering from Bipolar Disorder (BD) fulfilled also
diagnostic criteria for Borderline Personality Disorder (BPD),
and conversely, 18.5% of BPD patients for BD. However, these
data may not reflect true comorbidity given the overlap of their
phenomenological features (2–4). Of note, researchers have also
documented considerable rates of co-occurrence between BPD
and Major Depressive Disorder (MDD) or BD ranging from
as low as 3% to as high as 48% in clinical samples (5–8). The
high frequency of diagnostic co-occurrence and resemblance of
phenomenological features has led some authors to suggest that
BPD is part of the bipolar spectrum (9–13). Other experts in the
field have clearly opposed this notion (6, 14–17). Furthermore,
in the latter line, recent narrative reviews concluded that both
are distinct pathologies, even though they can be difficult
to distinguish due to a considerable overlap between both
conditions (3, 18). Differentiating BPD from BD-I appears
relatively straightforward, reflecting the common presence of
severe manic episodes, frequently with psychotic features, in
BD-I. By contrast, BD-II (alternating depressive and hypomanic
episodes) and BPD are frequently less precisely diagnosed, as
BD-II patients do not present with psychotic symptoms and
both share common clinical features, especially impulsivity
and emotional dysregulation (19). Furthermore, in BD-II there
is frequently subthreshold symptomatology between episodes
instead of full remission. Therefore, misdiagnosis in both
directions is common due to the uncertain boundaries between
both disorders (13) and shared “transdiagnostic” features (3).
The main objective of this systematic review is to synthesize
the evidence of whether clinical features, neuropsychological
and neuroimaging data comparing both conditions point toward
two distinct clinical entities or to them both belonging on a
continuum within the affective spectrum.
MATERIALS AND METHODS
Study Design
Using PubMed, PsycINFO and TripDataBase, we conducted a
systematic literature search of studies published from January
1980 to September 2019 based on PRISMA guidelines (20)
which compared clinical features, neuropsychological functions
and neuroimaging between BD and BPD. The search terms
were selected from the thesaurus of the National Library of
American Psychological Association (Psychological Index
Terms) and included the terms “borderline personality disorder,”
“BPD,” “bipolar disorder,” “BD,” “mania,” “hypomania,” “clinical
features,” “clinical symptoms,” “emotional dysregulation,”
“instability,” “temperament,” “mood,” “neuropsycho∗ ,”
“neurocognit∗ ,” “cogniti∗ ,” “impairment,” “deficit,” “functioning,”
“cognitive function,” “executive function,” “attention,” “memory,”
“working memory,” “neuroimaging,” “neuroimage.” The final
search equation was defined using the Boolean connectors
“AND” and “OR.”
The automatic search was later completed with a manual
search of the reference list of previous reviews and meta-analysis.
Titles, abstract, methods and results of the articles identified
were screened for pertinent information. The search did not
include any subheadings or tags (i.e., search fields “All fields”).
In accordance with Cochrane Handbook guidelines, due to the
significant heterogeneity and small number of the studies, a
formal quantitative synthesis (i.e., meta-analysis review) was not
possible to conduct (21), therefore a systematic literature review
was conducted.
The Newcastle-Ottawa Scale for assessing the quality of
non-randomized studies (22) was applied to each study
separately by AMR and BH. Discrepancies were resolved by a
third researcher, IGS. The completed PRISMA 2009 checklist
(20) and the Newcastle-Ottawa Scale (22) are included in
Supplementary Tables 1, 2.
Inclusion Criteria and Exclusion Criteria
The selection of the articles was carried out using the following
inclusion criteria: (i) observational studies published in peer-
reviewed journals, (ii) human studies, (iii) adult populations
(over 18 years), (iv) comparisons of a non-comorbid BD
and non-comorbid BPD group in terms of (v) clinical
features, (vi) neuropsychological functions or (vii) neuroimaging
performance. The criteria for exclusion were: (i) articles that
did not contain original research (i.e., reviews and meta-
analyses), (ii) controlled studies, (iii) qualitative designs, (iv)
empirical studies with quasi-experimental or single-case designs,
(v) unpublished studies, (vi) in youth and child population,
(vii) examined only pharmacological treatment trials. AMR
and BH conducted the first literature search and selected the
articles in an independent way. Discrepancies were resolved by
IGS and AVG.

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Massó Rodriguez et al.
FIGURE 1 | PRISMA flow diagram.
RESULTS
Eligibility of Studies
Using the search terms described above, the initial literature
search produced 551 articles. Titles were screened for eligibility
with the most relevant articles retained for abstract review. After
an initial review of relevance, 359 articles were retained for
further review of their titles and abstracts. BH, reviewer two,
also screened articles independently from AMR. Discrepancies
were resolved by two independent researchers, IG and AVG.
147 full-text articles were assessed for eligibility and a total
Frontiers in Psychiatry | www.frontiersin.org
Borderline Personality Disorder Bipolar Disorder
of 28 studies published since 1980 met the inclusion and
exclusion criteria: 19 focused on assessing clinical features (19,
23–39), six evaluated neuropsychological functioning (40–45)
and three assessed similarities and differences in neuroimaging
aspects (46–48). The study selection process can be seen
in Figure 1.
Clinical Features
Table 1 provides an overview of all studies mentioned in this
section which evaluate clinical features in BD and BPD.
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TABLE 1 | Clinical features between bipolar disorder and borderline personality disorder.

References Sample Variables Assessment instruments Main findings

Bayes et al. (19) DSM • Mood symptoms Structured Clinical Interview, - BPD patients compared to BD were significantly more
BD: 83 Self-report likely to report history of childhood sexual abuse,
BPD: 53 CLIN distant or rejecting parents and relationship difficulties.
EXTEND - BPD showed more suicide attempts, self-harming
BD:125 behavior and a younger onset of
BPD: 53 CLIN depressive symptoms.
STRICT
BD: 98
BPD: 53
Berrocal et al. (23) BD: 16 • Mood spectrum SCID-I, SCID-II, MOODS-SR - BD and BPD patients had significantly higher scores
BPD: 25 for lifetime mood symptomatology than HC.
HC:39
Pauselli et al. (24) BD: 16 • Clinical SCID-II, BPRS, PANSS - BD patients scored significantly higher than BPD on
BPD: 16 • Psychopathological features “euphoric manic” factor.
Vöhringer et al. (25) BD: 118 • Clinical features SCID-I, SCID-II, MDQ - The elevated mood, increased goal-directed activities
BPD: 52 • Mood state and periodicity are the strongest predictors in a mood
setting for BD.
- Racing thoughts, reduced need for sleep and an
increased self-confidence were the weaker predictors
of BD.
- Female gender predicted BPD in a mood
clinic setting.
di Giacomo et al. (26) BD: 113 • Depression SCID-I, SCID-II, HAM-D, - BD patients in manic or mixed state scored in a very
BPD: 248 • Anxiety HAM-A, YMRS, BPDSI-IV low range for depression and anxiety compared with
• Mania BPD.
- BD had low rates of impulsivity and anger control
whereas higher rates of irritability and disruptive-
aggressive behavior during acute manic phases.
- BPD group showed greater affective instability and
higher rate of suicidal and parasuicidal behaviors.
Emptiness and identity disturbance as key symptoms.
Perroud et al. (27) BD: 122 • History of SCID-I, SCID-II, CTQ - BPD patients had more severe childhood
BPD: 116 childhood maltreatment maltreatment, younger age of onset of mood disorders
• Clinical history and fewer overall mood episodes.
comorbid - BD patients had a higher history of psychotic
• Substance/Alcohol symptoms during a mood episode.
Use Disorder
Saunders et al. (28) BD: 20 • Mood state SCID-I, SCID-II, HAM-D, - BPD in comparison with BD and HC scored lower on
BPD: 20 • Clinical features YMRS, BIS-11 trait and state positive affect and higher on trait and
HC: 20 • Cognitive ability state negative affect, higher impulsivity and aggression
• Cooperation and reduced cooperative relationships.
- BD patients scored higher than HC in trait negative
affect, impulsivity and hostility and were more
cooperative than HC.
- BD and BPD had experienced significantly earlier
physical or sexual abuse than HC.
Bachetti et al. (29) BPD: 33 • Dysphoria NDS-I - Interpersonal Resentment dimensions of dysphoria
BD: 32 were greater in BPD than BD.
Eich et al. (30) BD-I: 17 • Temperament TEMPS-A, SCID-I, SCID-II - High cyclothymic temperament in BD and BPD.
BDII: 7 - BPD showed significantly lower levels of hyperthymia
BPD: 27 and higher levels of depressive temperament than BD.
- BD had significantly lower anxious and irritable-
explosive temperament than BPD.
Nilsson et al. (31) BD-I: 25 • Affective temperament SCAN, SCID-II, TEMPS-A, - BPD showed significantly higher scores on
BPD: 31 • Maladaptive YSQ-S3, BRManS, BRMeIS cyclothymic, depression, irritable and anxious
HC: 29 self- schemas temperament than BD and HC.
- BPD had lower scores on hyperthymic temperament
than BD and HC.
- BPD had higher scores on majority of maladaptive self-
schemas.
- BD showed higher scores than HC on cyclothymic
temperament and insufficient self- control.

(Continued)

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TABLE 1 | Continued

References Sample Variables Assessment instruments Main findings

Mneimne et al. (32) BD: 14 • Emotional instability MINI, SIDP-IV, ESM - With negative emotions, emotional instability has
BPD: 38 • Emotional reactivity transdiagnostic patterns in BPD and BD.
• Emotional intertia - BPD had heightened interpersonal reactivity to
negative emotions (guilt, shame and excitement).
- The emotional inertia of shame is a defining
characteristic of BPD.
- In BD dynamics of guilt and shame are not found.
Henry et al. (33) BD-II: 13 • Intensity shifts SIPD-R, SADS, ALS, AIM, - BD-II was characterized by shifts from euthymia to
BPD: 29 • Affective lability BDHI, BIS- 7B depression and elation, and from elation to depression.
• Impulsivity - BPD was characterized by shifts from anger/anxiety
• Aggressiveness to euthymia, presented significantly higher scores for
affective intensity, impulsivity and hostility.
- Significant interaction between the two disorders
between anxiety and depression.
Reich et al. (34) BDI-II: 24 • Intensity shifts SCID-I, DIB-R, DIP-IV, AIM, - BPD showed significantly more frequent and intense
BPD: 29 • Frecuency shifts ALI-BPD, ALS affective shifts between euthymia-anger, anxiety-
depression and depression- anxiety, and more intense
shifts from euthymia to anxiety.
- BD showed significantly more frequent and intense
shifts from euthymia to elation.
Bayes et al. (35) BD: 83 • Emotion regulation Semi-structured interview, - BPD displayed a higher number of maladaptive
BPD: 53 • Cognitive emotion MINI, DIP-IV, DERS, CERQ emotion regulation strategies.
• Regulation - Adaptive emotion regulation strategies were superior
in BD group.
Fletcher et al. (36) BD-II:24 • Emotion MINI, DIPD-IV, CERQ, DERS, - BPD significantly more likely than BD to use
BPD: 24 • Perceived parental style MOPS, QIDS-SR maladaptive emotion regulation strategies and
• Depressive symptoms less likely to use adaptive ones.
- BPD patients scored significantly higher on majority of
perceived parental style sub-scales than BD.
- Dysfunctional maternal relationships related to
maladaptive emotion regulation strategies in BPD.
- Dysfunctional paternal relationships significantly
associated with emotion regulation strategies in both
clinical groups.
Kramer (37) BD: 25 • Coping processes SCID-II, MINI, SCL-90-R, - BPD and BD had significantly lower coping functioning
BPD: 25 CAPRS than HC in terms of competence and resources.
HC: 25 - BPD patients had significantly lower coping
functioning than BD patients in autonomy.
Bøen et al. (49) BD-II: 20 • Mood criteria MINI, SCID-II, MADRS, - BPD patients showed higher levels of self-reported
BPD: 25 • Impulsivity YMRS, CTQ, PDQ-4, NEQ, impulsivity than BD-II patients, who in turn showed
HC: 44 AUS, DUS, UPPS more impulsivity than HC.
- In BD-II group, increased impulsivity was strongly
associated with depressive mood state and
moderately with childhood trauma.
- No association between impulsivity and childhood
trauma in the BPD group.
Richard-Lepouriel BD: 276 • Impulsivity SCID-II, DIGS, BIS-10, CTQ - BPD and BD: impulsivity associated with adverse
et al. (38) BPD: 168 • Traumatic childhood experiences
HC: 47 childhood experiences - Higher impulsivity in BPD than BD and HC
- BPD: Impulsivity is an intrinsic trait
- BD: impulsivity is environmentally driven and
associated with adverse traumatic
childhood experiences
Mazer et al. (39) BPD: 20 • Emotional abuse SCID-II, BAI, BDI-II, BHS, - BPD patients had a higher severity of depressive,
BD: 16 • Physical abuse BSI, YMS, CTQ suicidal ideation, hopelessness, anxiety and impulsivity
HC: 15 • Sexual abuse symptoms than BD.
• Emotional neglect - BPD experienced more severe early distress compared
• Physical neglect to BD patients.
• Symptomatology - A history of ELS in BPD and BD.
- Higher proportion of ELS in BPD than BD and HC
group.

(Continued)

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TABLE 1 | Continued

References Sample Variables Assessment instruments Main findings

- Emotional abuse, emotional neglect and physical

neglect predominated in BPD.
- Physical and sexual abuse, only up to moderate
severity, with no difference between clinical groups.

ADHD, Attention Deficit Hyperactivity Disorder; AIM, Affective Intensity Measure; ALI-BPD, Affective Lability Interview for Borderline Personality Disorder; ALS, Affective Lability Scale;
ASQ, Attachment Style Questionnaire; AUS, Alcohol Use Scale; BAI, Beck Anxiety Inventory; BD, bipolar disorder; BDHI, Buss-Durkee Hostility Inventory; BD-I, Bipolar Disorder Type-1;
BD-II, Bipolar Disorder Type- 2; BDI-II, Beck Depression Inventory Second Edition; BHS, Hopelessness Scale; BIS-11, Barrat Impulsiveness Scale; BPD, Borderline Personality Disorder;
BPDSI-IV, The Borderline Personality Disorder Severity Index-IV; BPRS, Brief Psychiatric Rating Scale; BRMaS, Beck Rafaelsen Mania Scale; BRMelS, Beck Rafaelsen Melancholia Scale;
BSI, Suicidal Ideation Scale; CAPRS, Coping Action Patterns Rating Scale; CERQ, Cognitive Emotional Regulation Questionnaire; Clin extend, clinical extend; Clin strict, clinical strict; CTQ,
Childhood Trauma Questionnaire; DERS, Difficulties in Emotion Regulation Scale; DIGS, Diagnostic Interview for Genetic Studies; DIPD-IV, Diagnostic Interview for Personality Disorders
DSM-IV; DIS, Diagnostic Interview Schedule; DSQ, Defense Style Questionnaire; DSM, Diagnostic and Statistical Manual of Mental Disorders; DUS, Drug Use Scale; ELS, Early Life
Stress; ESM, Experience Sampling Methodology; HAM-A, Hamilton Anxiety Rating Scale; HC, healthy control; HDRS, Hamilton Depression Rating Scale; IAS-R, Interpersonal Adjective
Scales-Revised; MADRS, Montgomery- Åsberg Depression Scale; MDD, Major Depressive Disorder; MDQ, Mood Disorder Questionnaire; MINI, Mini-International Neuropsychiatry
Interview; MOODS-SR, The Mood Spectrum Self-Report; MOPS, Measure of Parental Style; NDS-I, Neapen Dysphoria Scale- Italian Version; NNEQ, Network Entry Questionnaire;
OPD, Other Personality Disorders; PANSS, Positive and Negative Syndrome Scale; PDQ-4, Personality Diagnostic Questionnaire Version 4; PIP, Physician Interview Program; QIDS-
SR, Quick Inventory of Depressive Symptoms Self-Report; RIT, Rorschach Inkblot Test; SADS, Schedule for Affective Disorders and Schizophrenia; SASB, Structural Analysis of Social
Behavior Rating Scales; SCAN, Schedules for Clinical Assessment in Neuropsychiatry; SCID-I, Semi-structured Clinical Interview for DSM Axis 1; SCID-II, Semi-structured Clinical
Interview for DSM Axis II; SCL-90-R, Symptom Checklist 90; SIPD-R, Structured Interview Personality Disorders for DSM-III-R; SIPD-IV, Structured Interview Personality Disorders for
DSM-IV; TCI, Temperament and Character Inventory; TEMPS-A, Temperament Evaluation of the Memphis; Pisa, Paris and San Diego Autoquestionnaire; UPPS, The UPPS Impulsive
Behavior Scale; YMS, Young Mania Scale; YMRS, Young Mania Rating Scale; YSQ-S3, Young Schema Questionnaire-version 3.

Affective Symptoms was characterized by a significantly earlier onset of depressive

Mood swings are prominent clinical features of both disorders,
with affective symptoms of particular interest when comparing
BPD and BD-II. In our review, eight clinical studies investigated
general psychopathology comparing BPD and BD, in most cases
without a healthy control group for comparison. Symptoms
of mania and depression were evaluated mainly through
clinical judgment, and other symptoms (e.g., dysphoria)
through self-report.
Firstly, Berrocal et al. (23) found both disorders showed
elevated lifetime mood symptomatology as compared to Healthy
Controls (HC) but no significant difference between them.
Four studies compared both disorders in terms of manic
symptoms (23–26). Berrocal et al. (23) found the differences
in manic symptoms between bipolar patients and BPD were
not statistically significant. Conversely, three of these found
that these symptoms could differentiate the two disorders (24–
26). Specifically, Pauselli et al. (24) found in an acute inpatient
sample that manic-psychotic symptoms differentiated BD-I from
BPD. Vöhringer et al. (25) in an outpatient sample, found
that elevated mood, increased goal-directed activities, racing
thoughts, reduced need for sleep, increased self-confidence and
episodicity predicted BD but not BPD. Similarly, di Giacomo
et al. (26) found that BD patients in mixed or manic phases
showed significantly more manic symptoms than BPD patients.
At the other end of the mood spectrum, six studies compared
the two disorders in terms of depressive symptoms (19, 23,
24, 26–28). Of these, two studies (23, 24) which did not state
the BD phase, found no significant differences in depressive
symptoms between the two disorders, including symptoms of
inhibited depression or mixed features with anxiety, depression
and suicidality. In contrast, di Giacomo et al. (26) found fewer
anxiety and depressive symptoms in BD patients in manic or
mixed states, while BPD patients had a wider range of anxiety
and depressive symptoms. Similarly, two studies found BPD
episodes than BD (19, 27), but BPD patients had fewer overall
episodes and less history of psychotic symptoms during a mood
episode. Furthermore, Saunders et al. (28) found that BPD
patients had more depressive symptoms than euthymic BD
patients and HC.
Finally, one study (29) compared the two disorders in
terms of dysphoria. This study demonstrated that total score
for dysphoria, and subscales of irritability and interpersonal
resentment, were significantly higher in BPD patients than in BD.
Thus, in brief, manic features, including psychotic symptoms,
can indicate a diagnosis of BD-I and distinguish BD from BPD.
Otherwise, anxiety, depressive symptoms and dysphoria can be
found in both disorders but may be more persistent, intensive
and with an earlier onset of depressive symptoms in BPD than
in BD.
Affective Temperament
The affective temperament is described as the set of behavioral
traits, stable throughout the life course and with a biological basis,
that reflect styles of affective reactivity including activity levels,
mood rhythms and patterns of cognitive functioning (50–52).
Assessed by the studies in this review by self-report measures, it
has been discussed as a neurobiological underpinning of both BD
and BPD (29).
Two studies compared the affective temperament of BPD
with that of BD (30, 31). Eich and colleagues (30) suggested
that BD and BPD share a common temperamental diathesis,
including similar levels of abnormal cyclothymic temperament,
reactive instability, anxious-dependent and avoidant attitudes,
and impulsive reactive behavior. The other study (31) found
that, while these disorders share abnormal temperamental traits,
BPD patients showed a greater severity and scored significantly
higher in terms of cyclothymic, depressive, irritable and anxious

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Massó Rodriguez et al.
temperament than BD patients, whereas BD patients scored
significantly higher in the hyperthymic temperament.
In conclusion, both conditions share high scores in various
temperamental traits, but with a greater severity in cyclothymic,
depressive, irritable and anxious temperament in patients
with BPD, while the BD profile is characterized more by a
hyperthymic temperament.
Emotion Dysregulation
Emotion dysregulation or affective instability is defined as
the inability to flexibly respond and manage emotions (53)
which interfere with appropriate goal-directed activity (54).
Many researchers have characterized BPD and BD separately
in terms of heightened reactivity and instability of negative
emotion (55–58). In this review, seven studies reviewed affective
instability/emotional dysregulation, with a set of structured
diagnostic interview and self-rating scales, comparing BPD with
BD patients (26, 32–37).
Although findings from four studies showed similarly high
levels of affective lability comparing BPD to a mixed sample
of BD-I and BD-II (26, 32–34), the results revealed also some
different pattern in both disorders. Accordingly, Mneimne et al.
(32) found that, while emotional instability is a shared trait,
in terms of heightened instability of anger and irritability and
heightened inertia of irritability, only BPD is characterized by
emotional reactivity to interpersonal challenges, heightened for
guilt, shame and excitement, irritability and happiness. As well,
shifts from anger and anxiety to euthymia were associated with
BPD, whereas shifts from euthymia to depression and elation,
and shifts from depression to elation, were characteristic of BD
patients (33, 34). Furthermore, BPD patients showed higher
affective intensity (33, 34) and higher affective instability than BD
patients in a mixed or manic state (26).
Two other studies analyzed similarities and differences
between emotion regulation strategies in both disorders (35, 36).
Both studies found that BPD subjects displayed a higher number
of maladaptive emotion regulation strategies than BD patients,
such as deficits in non-acceptance of emotional responses, limited
access to emotion regulation strategies, lack of clarity around
emotions and emotional awareness, difficulties in controlling
impulsive behavior and a tendency to self-blame, catastrophize
and blame others. BPD patients were also less likely to use
adaptive strategies such as planning, reappraisal and putting
things into perspective compared with those with a BD disorder.
However, neither of these two studies compared patients to HC.
Coping, as a specific operationalization of affect regulation,
was reviewed in one study (37). Findings showed that while both
BPD and BD patients both had difficulties in the coping domains
of competence and resources, BPD patients have a specific lack
of adaptive autonomy coping patterns, such as negotiation and
accommodation, as compared to BD patients.
In summary, the results show that emotional dysregulation
or affective instability appear to be an overlapping symptom,
but it is more pronounced in BPD and pathways are different.
Furthermore, BPD have a higher number of maladaptive emotion
regulation strategies than BD patients.
Frontiers in Psychiatry | www.frontiersin.org
Borderline Personality Disorder Bipolar Disorder
Impulsivity
Impulsivity or impulsiveness is a core feature of BPD and
BD and may represent a way of managing negative emotions
(9). It reflects the tendency to act on a whim, displaying
behavior characterized by little or no forethought, reflection, or
consideration of the consequences (59). Nine studies investigated
impulsiveness in BPD and BD patients using clinical interviews
and self-report measures (24, 26, 28, 31, 33, 35, 36, 38, 49).
Five of these studies directly compared impulsivity between
BD and BPD and all of them found that BPD patients had
elevated impulsivity compared to BD patients (24, 26, 33, 34, 36).
Otherwise, four studies comparing BD and BPD patients with
HC found that while BD patients had lower impulsivity than
BPD, they showed significantly higher impulsivity than HC (28,
31, 38, 49). Further analysis of impulsivity profiles found that
BPD patients demonstrated high levels of impulsivity as a trait,
unrelated to current mood state, while impulsivity in the BD-II
group is present as both a trait and strongly related to current
depressive mood state (49). BPD patients had higher scores in all
impulsivity dimensions except in novelty seeking (38). Both Bøen
et al. (49) and Richard-Lepouriel et al. (38) found that impulsivity
was correlated with levels of childhood trauma in BD, while in
BPD it was not.
Similarly, three studies compared both disorders in terms of
aggression, closely related to impulsivity (26, 28, 33). Two studies
showed that BPD patients are more hostile and aggressive than
euthymic BD patients and HC (28, 33). However, a further study
found that BD patients showed low “anger-control” but high
“irritability” and “disruptive-aggressive behavior” during manic
or mixed phases (26).
Along these lines, two studies carried out into behaviors
related to suicide and self-harm found that BPD patients show
a significantly higher rate of self-injury, suicidal and parasuicidal
behaviors than BD (19, 26).
In summary, there is strong evidence for a higher
impulsiveness in BPD than in BD, which is again more
pronounced when compared to HC. Whereas, in BPD high levels
of impulsivity were described as a trait, in BD impulsiveness was
potentially more related to affective episodes. Both disorders
were related with aggressive behavior, which was again more
intense in BPD.
Childhood Trauma
History of childhood trauma has been reported among the
etiological factors of BD (60) and BPD (61). Five retrospective
studies were carried out to investigate different forms of
traumatic childhood experiences in both disorders using
structured clinical interview and self-report questionnaires.
Five studies explored childhood trauma rates in BD
and BPD patients (19, 27, 28, 39, 49). While both patient
groups had experienced significantly more trauma than
HC (28, 39), results point to severity of childhood trauma
being more marked in BPD patients (19, 27, 28, 39, 49).
In detail, Bayes, McClure et al. (19) found BPD patients
were significantly more likely to report childhood sexual
abuse, parental indifference, maternal abuse and over-
control, developmental trauma, childhood depersonalization,
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Massó Rodriguez et al.
distant/rejecting parenting. Similarly, Mazer et al. (39)
found that emotional abuse, emotional neglect and physical
neglect predominated in BPD, differentiating it from BD.
Otherwise, Bøen et al. (49) found more severe childhood
maltreatment in BPD. Conversely, Saunders et al. (28) found
no significant difference between physical and sexual abuse
suffered between both groups, although rates were higher in the
BPD group.
Interestingly, Fletcher et al. (36) showed that maladaptive
strategies and maladaptive emotion regulation were linked to
parental style in both disorders, particularly in BPD, but with
differences in terms of the type of trauma and its consequences.
Therefore, dysfunctional maternal relationships characterize
BPD, whereas dysfunctional paternal relationships led to emotion
regulation deficits in both disorders. Furthermore, maternal
abuse was associated with increased self-blame, while maternal
over-control was associated with an increased tendency to
catastrophize and blame others in BPD. Otherwise, paternal
abuse was associated with a reduced use of acceptance strategies
in BPD, while paternal over-control was negatively associated
with the use of positive refocusing and to put things into
perspective and a reduced impulsive control behavior in patients
with BD-II. Finally, paternal relationships characterized by
indifference were relevant to both groups, but in BPD this
was associated with an increased tendency to blame others,
whereas in BD-II it was associated with an increased tendency
to ruminate.
Therefore, to summarize, both BD and BPD patients
are more likely to have suffered childhood trauma
than HC, but with BPD patients being more affected
than BD.
Relationships With Self and Others
Three clinical studies compared BD and BPD in terms of different
aspects of relationships with others (19, 28, 31) using interviews
and self-report measures. Two studies found that BPD patients
had significantly more difficulties in interpersonal relationships
as compared to BD patients (19, 28). Specifically, Bayes,
McClure et al. (19) found that two personality characteristics,
“relationship difficulties” and “sensitivity to criticism by others,”
distinguished BPD patients from BD patients and were the
most consistent predictors of BPD. Saunders et al. (28) found
that BPD patients showed reduced cooperation compared to
BD patients and HC, and had difficulties in establishing and
maintaining reciprocally cooperative relationships. In contrast,
the results for euthymic BD patients showed they were capable of
developing cooperative relationships and were marginally more
cooperative than HC.
Additionally, Nilsson et al. (31) found that BPD patients
endorse negative and distressing beliefs about themselves and
their relationships with others compared to HC and BD group.
In summary, the evidence shows that BPD patients have
more negative attitudes toward others and self, and more
conflictive interpersonal relationships, which may distinguish
BPD from BD.
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Borderline Personality Disorder Bipolar Disorder
Neuropsychological Functions
Six studies investigated differences in executive functioning,
attention and impulsivity between BD and BPD patients (40–45)
and compared to HC data (Table 2).
Akbari et al. (40) found that euthymic patients with BD-II and
BPD had a poorer performance than HC in most neurocognitive
domains, specifically in cognitive flexibility and set-shifting,
decision-making, sustained and selective attention and problem-
solving. In addition, BPD patients had more elevated response
inhibition deficits than BD-II patients, which may contribute to
greater impulsivity and poor affect regulation.
Another study compared errors made on the Continuous
Performance Test-II (CPT-II) related to impulsivity and
attention in both disorders (41). The authors found both clinical
groups displayed neuropsychological deficits as compared to
HC, but that the pattern differed according to each disorder.
Processing speed was a key differentiator, with BPD patients
showing significantly faster processing speed which was related
to impulsivity, and a reduced ability to discriminate stimuli,
probably related to selective attention. On the other hand,
BD patients showed greater overall cognitive impairment, with
slower processing speeds and deficits in sustained attention.
These results support the findings from studies into clinical
features indicating impulsivity as a trait marker of BPD. BPD
patients are characterized by high levels of motor impulsivity
and non-planning impulsivity, while BD patients have increased
levels of attentional impulsiveness (41).
Gvirts et al. (42) used the Cambridge Neuropsychological Test
Automated Battery to compare sustained attention, problem-
solving, planning, strategy formation, cognitive flexibility and
working memory. Similar to the previous study, the authors
found deficits in both disorders which followed divergent
patterns. BPD patients showed greater deficits in planning
compared to BD and HC, and in problem-solving only with
the HC. Otherwise, BD patients showed significant deficits in
strategy formation and increased execution time compared to
BPD patients and HC. Both BPD and BD patients showed deficits
in sustained attention as compared to HC.
Another study compared interference control between BPD,
BD and HC assessing the ability to exert control over interference
arisen from semantic memory or from distracting perceptual
information (43). They found that BD and BPD shared a
common impairment in the first task, but both disorders retained
intact control over perceptual interference, leading the authors
to conclude that similar cognitive functioning may underlie
different disorders and symptomatology.
Saunders et al. (44) carried out a study to investigate the speed
and accuracy of sensorimotor performance in BD patients, BPD
patients and HC. They found no significant differences between
any group in any task. However, BPD patients showed transitory
post-error slowing.
Finally, Saunders et al. (45) carried out another study to
evaluate decision-making in BPD patients, euthymic BD patients
and HC. They found that BPD is associated with impaired
decision-making, specifically in problems attending and using
reinforcement cues to identify negative outcomes. They paid
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TABLE 2 | Neuropsychological differences between bipolar disorder and borderline personality disorder.

References Sample Variables Assessment instruments Main findings

Akbari et al. (40)
Feliu-Soler et al. (41)
Gvirts et al. (42)
Lozano et al. (43)
Saunders et al. a (44)
Saunders et al. (45)
BPD: 35 • Cognitive flexibility WCST, IGT, SCWT, ToL, CPT, - BPD and BD-II had poorer
BD II: 5 • Set-shifting WAIS. performance than HC on most
HC: 30 • Response neurocognitive domains.
inhibition - BPD patients had more elevated
• Problem solving response inhibition deficits and more
• Decision-making impulsivity than BD-II patients.
• Sustained attention - BPD and BD-II patients had poorer
• Selective attention performance in planning and
problem-solving than HC.
BD-I: 34 • Neuropsychological DIB-R, CPT-II - BPD had reduced ability to
BD-II: 4 performance discriminate stimuli and faster
BPD: 35 processing time.
HC: 70 - BD showed significantly slower
processing time.
- Both clinical groups showed more
omission, comission and
perseveration errors than HC.
BD-I: 26 • Neuropsychological CGI, GAF, CANTAB - BPD showed deficits in planning
BD-II: 4 performance compared to BD and HC and in
BPD: 32 • Functionality problem-solving compared to norms
of HC.
- BD had significant deficits in strategy
formation and increased execution
time compared to BPD and norms
of HC.
BD: 19 • Social, GAF, HSCT, Flanker task - BD and BPD showed significantly
BPD: 20 occupational and poorer interference control with more
HC: 19 psychological functioning context-related errors than HC.
- Interference score correlated with
illness duration in BD.
BD I: 20 • Clinical features BIS- 11, Buss- Perry Q, Ravens’ - BPD patients showed transitory
BPD: 20 • Neurocognitive matrices, Reaction time task post-error slowing than BD and HC.
HC: 20 performance
BD: 20 • Impulsivity Raven’s matrices, BIS-11, - BPD were associated with problems
BPD: 20 • Decision-making Buss- Perry Q, Risk choice task attending to and using explicit
HC: 20 reinforcement cues compared to BD
or HC.
- BPD had alterations in the processing
of information about potential gains
and losses compared to the other
groups.
- BD group was intermediate between
HC and BPD in sensitivity to
high-loss risks.

BD, bipolar disorder; BD-I, Bipolar Disorder Type-1; BD-II, Bipolar Disorder Type-2; BIS-11, Barrat Impulsiveness Scale; BPD, Borderline Personality Disorder; CANTAB, Cambridge
Neuropsychological Test Automated Battery; CGI, Clinical Global Impressions; CPT, Continuous Performance Test; CPT-II, Conner’s Continuous Performance Test; DIB-R, Diagnostic
Interview for Borderline-Revised; GAF, General Assessment of Functioning; HC, healthy control; HSCT, Hailing Sentence Completion Test; IGT, Iowa Gambling Task; SCWT, Stroop
Color- Word Interference Test; ToL, Tower of London; WAIS, Weschler Adult Intelligence Scale; WCST, Wisconsin Card Sorting Test.

significantly less attention to prospective losses; thus BPD is
related to engagement in harmful and risky behaviors. The BD
sample showed no impairments in decision-making as compared
to the HC participants, but were intermediate between the
other groups in their sensitivity to high-loss risks. However, in
this study the potential presence of comorbid Attention Deficit
Hyperactivity Disorder (ADHD) is a possible confounder.
To conclude, evidence from the six neuropsychological
studies shows that both disorders overlap and differ
in neuropsychological deficits. BPD and BD-II patients
had in common poorer performance in their planning
and problem-solving performance, when compared to HC.
Whilst deficits related to motor and non-planning impulsivity,
planning, and difficulty attending to specific cues are more
prevalent in BPD patients, deficits related to processing speed
and strategy formation and increased levels of attentional
impulsiveness are indicative of BD patients.
Neuroimaging
Neuroimaging studies are increasingly used to characterize
psychiatric disorders since they provide precise and direct
information on the structure and functioning of the brain, which

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Massó Rodriguez et al.
can be compared in different psychiatric disorders. Three studies
revised neuroimaging features in BPD and BD as compared to
HC (46–48) (Table 3).
Rossi et al. (46) carried out a structural Magnetic Resonance
Imaging (MRI) study to explore volumetric differences in
hippocampal subdivisions in BPD and BD as compared with
HC using a three-dimensional mapping method. Results showed
that both clinical groups had smaller hippocampal volumes as
compared to HC; however, two distinct patterns of gray matter
(GM) loss were found in each of the clinical conditions. More
specifically, the hippocampal surface maps showed that the CA1
region and the subiculum were bilaterally atrophic in BPD,
whereas in bipolar subjects there was a significant alteration in
the right dentate gyrus.
In order to extend the previous analysis, the same research
team carried out another structural study using a Voxel-Based-
Morphometry (VBM) and Regional Volumes (RV) analysis
(47). The VBM analysis showed again distinct patterns of
GM alterations for each condition. BD subjects presented
smaller GM volume in the temporal and frontal lobes, and the
precuneus, cerebellum and thalami regions compared to the HC.
Otherwise, BPD subjects showed smaller GM volume in the
hippocampus, the amygdala and the prefrontal, frontal, parietal
and occipital lobes. However, the RV analysis showed that
both disorders presented smaller global GM regional volumes
compared with HC. The results also provided evidence that
regions selectively observed in BPD are strongly correlated
with deficits in emotional processing (hippocampus, middle
and inferior temporal gyrus). Furthermore, the RV analysis
showed that BD had less GM volume in the frontal, limbic,
parietal and cerebellar regions compared with BPD. The authors
hypothesized that BD might present a relatively diminished pre-
frontal modulation of subcortical and medial temporal structures
within the limbic system (amygdala and thalamus), resulting in
dysregulation of mood.
Likewise, Das et al. (48) carried out a study in order to
understand how impaired functional connectivity correlated with
emotion dysregulation in both disorders. Results demonstrated
that BD and BPD can be differentiated on the basis of resting state
functional connectivity among networks involved in detecting
social salience, self-referential processing and emotional
regulation. Specifically, BD patients displayed increased
connectivity, compared to both BPD and HC, in coupling of
social salience (SS)-ventral medial prefrontal cortex (vmPFC)
and default mode (DM)-precuneus networks. Conversely,
BPD patients displayed decreased connectivity as compared
to the rest of the groups in the coupling of SS-precuneus and
SS-right fronto-parietal (RFP) networks that were responsible
for self-referencing information and which were related to the
failure to integrate information from the environmental stimuli
and internal representation, linked to impulsive behaviors
and self-harm.
In conclusion, both structural and functional neuroimaging
findings suggest that a number of areas of overlap exist; however,
structural and functional findings also suggest neuroanatomical
differences between BPD and BD which could explain the
clinical symptomatology presented in both disorders, especially
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Borderline Personality Disorder Bipolar Disorder
related with emotional processing and emotional dysregulation.
Nevertheless, the sample size for significance of these studies
are limited, meaning a firm confirmation about neuroanatomic
differences still cannot be drawn.
A summary of the specific and shared features of both
disorders can be seen in Table 4.
DISCUSSION
To our knowledge, this is the first systematic review of
clinical and neurobiological studies which directly compare
patients with BPD and BD. A total of 28 studies met our
inclusion criteria, 19 of them comparing clinical features,
six comparing neuropsychological performance and three
comparing neuroimaging abnormalities. Our review shows that
both disorders can be distinguished in terms of distinct clinical
variables, but also share a variety of psychiatric symptoms.
Interestingly, most of the shared symptoms seem more persistent
and intense in BPD. Furthermore, while neurobiological data
suggest differences and similarities between both disorders, the
data from the neuropsychological and especially neuroimaging
studies are currently limited. This means we cannot definitively
answer our research question of whether both conditions belong
to the same affective continuum, or whether they are separate
nosological entities, with BD a mood disorder and BPD a
personality disorder.
Most clinical variables investigated were present and common
in both disorders, but there exists a clear tendency that various
symptoms are more intense in BPD and some variables differ in
further phenomenological and state/trait aspects. For instance,
BD patients present more mixed or manic symptoms than
BPD patients. A manic state, related to euphoric mood with
psychotic symptoms, increased goal-directed activities and mood
episodicity, seems specific to distinguish BD-I from BPD (3,
24, 25). Of note here, affective instability in BPD shifts from
anger and anxiety to euthymia, whereas in BD it shifts from
euthymia to depression and elation, and from depression to
elation (33, 34, 62). What is more, the temporal course of
emotional dysregulation differs between the two disorder: in
BPD mood tends to change over hours, usually in response
to interpersonal conflict, while in BD it requires at least a
4-day course to be described as hypomania and the triggers
are less clear (63). This distinct pattern might represent a
relevant underpinning for the differentiation between BD-I and
BPD. Interestingly, patients with BPD show more maladaptive
regulation strategies in their affective instability than BD patients.
Unlike BPD, impulsivity is not a diagnostic criterion of BD, but
it could be related to disinhibition, present during manic or
mixed episodes (64, 65) and also persistent during euthymia (66)
yielding problematic behaviors in both disorders such as self-
injury, suicidality or substance abuse (66, 67). Results showed
differences in profile impulsivity between both disorders, and
in this regard our neuropsychological findings are of note. As
stated, BPD patients are characterized by high levels of motor
impulsivity and non-planning impulsivity while BD patients have
increased levels of attentional impulsiveness (41). This finding
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TABLE 3 | Neuroimaging results between bipolar disorder and borderline personality disorder.

References Sample Variables Method Main findings

Rossi et al. (46) BD: 15 • Hippocampus volumetry ROI analysis - Smaller hippocampal volumes in both
HC for BD: 15 clinical groups than HC but with
BPD: 26 distinct patterns of gray matter loss
HC for BPD: 26 (subiculum and right dentate gyrus).
Rossi et al. (47) BD: 14 • Brain volumetry VBM VBM
HC for BD: 14 RV analysis - BD vs. HC: Smaller GM in temporal
BPD: 26 and frontal lobes, precuneus,
HC for BPD: 26 cerebellum and thalamus.
- BPD vs. HC: Smaller GM in
hippocampus, amygdala, prefrontal,
parietal and occipital lobes.
RV
- BD, BPD vs. HC: Smaller global GM
- BD vs. BPD: less GM volume in the
frontal, parietal, limbic and
cerebellar regions.
Das et al. (48) BD: 16 • Functional connectivity Resting state - BD and BPD were differentiated on
BPD: 14 the basis of resting state functional
HC: 13 connectivity among networks.
- BD had an increased connectivity
in networks related to social
understanding, but diminished
emotional clarity.
- BPD displayed decreased
connectivity in networks responsible
for self-referencing information and
failure to integrate information.

BD, bipolar disorder; BPD, Borderline Personality Disorder; HC, Healthy Control; ROI, Region of Interest; VBM, Voxel-Based-Morphometry; RV, Regional volumes.

could be related with cognitive execution. Along these lines,
BPD patients are characterized by a faster processing speed and
a reduced ability to discriminate stimuli and to use cues to
identify negative outcomes, while in BD there are more deficits
in sustained attention. Therefore, impulsivity can be considered
more as a trait in BPD, while in BD it can be considered more as
a state and related to affective episodes. Interestingly, impulsivity
in BPD tends to decrease over time while affective characteristics
and relationship problems are more likely to continue, unlike
BD. Further evidence which appears to support two different
disorders might be that BPD patients have an emotionally
noxious sense of self, more negative attitudes toward others and
self, and more conflictive interpersonal relationships than bipolar
patients. There is an extensive literature that has attempted to
clarify the nosological controversy between bipolar disorder and
borderline personality disorder. While older articles support the
vision of a mood spectrum (9–13), others, including more recent
ones, tend toward the idea that they are two different entities
(6, 14–17). Our findings to this point represent a tendency so
far toward a more dichotomous approach to both disorders,
especially to BD-I and BPD. Putting our findings into the context
of reviews which included data from studies which investigated
the disorders separately rather than directly comparing them,
our findings that mood lability, emotional dysregulation and
impulsivity are symptoms common to both disorders (although
their presentation and time course may be different), but that
there are differences in terms of manic and psychotic symptoms
and past abuse, are in line with recent reviews (3, 18). Again using
data from studies that were not a direct comparison, previous
authors have also found differences in parasuicidal self-harm,
incidence of suicide, and treatment response, and more data to
support a difference in cognitive deficits, as well as differences in
bipolar family history suggesting a stronger genetic component
in BD (3, 16). Indeed, the heritability rate in bipolar disorder
has been shown to be greater than in BPD (between 0.69 and
0.80 (68) compared to between 0.35 and 0.80 (69, 70). Finally,
a recent narrative review by Sanches (18) also summarizes that
the two conditions are separate, but also states: “It is possible
that some forms of bipolar disorder are virtually identical to
BPD from a phenotypical standpoint, making both conditions
difficult to distinguish at times, particularly given the absence of
well-established biomarkers from both conditions.”
In this sense, we detected various clinical variables which
are prevalent and common in both disorders and differ in
intensity only. This observation could serve as an argument
to place both conditions along a continuum of the affective
spectrum, as proposed by Akiskal (9), or following Sanches (18)
who suggested that some forms of BD are identical to BPD
from a phenotypical standpoint. Clinical variables common to
both are aggressive behavior and suicidal ideation. Furthermore,
symptoms in both disorders include depressive and anxious
symptoms, dysphoria, and hypomanic mixed states. The latter
are defined by high and low symptoms concurrently present in
the same episode (10, 71). Whilst we have evidence to be able

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TABLE 4 | Specific and shared features of bipolar disorder and borderline personality disorder.

Feature Bipolar disorder Borderline personality disorder Bipolar disorder and borderline personality disorder

Manic-psychotic BD- I: Manic-psychotic symptoms: Less history of psychotic symptoms

symptoms - elevated mood during a mood episode.
- increased goal- directed activities
- racing thoughts
- reduced need for sleep
- increased self-confidence
- mood episodicity
Affective symptoms BD-I: a wider range of anxiety and - An earlier onset of depressive episodes Mixed features with anxiety, depression and suicidality
depressive symptoms. than BD. common to both disorders
- Fewer overall episodes than BD.
- Higher rates of dysphoria, irritability and
interpersonal resentment.
Temperament Higher hyperthymic temperament. Greater severity of cyclothymic, Common temperamental diathesis
depressive, irritable and anxious - abnormal cyclothymic temperament
temperament than BD. - reactive instability
- anxious- dependent and avoidant attitudes
- impulsive reactive behavior
Emotional instability - At least a 4-day mood course - Mood tends to change over hours Emotional instability is a shared feature but expressed
- Shifts from euthymia to - Shifts from anger and anxiety to euthymia differently in each disorder
depression/ elation - Emotional reactivity to interpersonal
- Shifts from depression to elation challenges
- Triggers of emotional instability not clear
Impulsivity - Impulsivity is related to current - Higher levels of impulsivity, as a trait Impulsivity a shared feature with a different expresión in
mood state - More hostile and agressive each disorder
- Related to disinhibition - Higher rate of self-injury, suicidal and
parasuicidal behavior
- Tends to decrease over time
Coping strategies Higher number of adaptive strategies Higher number of maladaptive emotion Shared difficulty in coping but difficulties are in different
than BPD: regulation strategies than BD: areas
- planning - non-acceptance of emotional reponses
- reappraisal - limited access to emotion regulation
- puting things into perspective. strategies
- ruminate - lack of clarity around emotions and
emotional awareness
- difficulties in controlling impulsive
behavior
- a tendency to self-blame catastrophize
and blame others.
Childhood trauma Higher rates of childhood trauma than in More likely to report: A shared feature, more marked in BPD
controls - childhood sexual abuse
- parental indifference
- maternal abuse and over-control
- developmental trauma
- childhood despersonalization
- distant/rejecting parenting
Neurocognitive - Slow processing speed More elevated response inhibition deficits BD-II and BPD have shared difficulties in these
deficits - Deficits in sustained attention than BD-II. neurocognitive domains:
- High levels of attentional impulsiveness. - Fast processing speed - cognitive flexibility and set-shifting
- Significant deficits in strategy formation. - Reduced ability to discriminate stimuly - decision- making
- Sensitivity to high loss risks - High levels of motor impulsivity and - sustained and selective attention
non-planning impulsivity. - problem- solving
- Deficits in planning - impairment in exerting control over interferences arising
- Problems attending to and using from semantic memory
reinforcement cues to identify negative - Evaluating decisión making
outcomes
Neuroimaging data - Significant alteration in the right - CA1 region and the subiculum were Smaller hipocampal volumes than healthy controls and
dentate gyrus. bilaterally atrophic. functional connectivity deficits
- Small volume in the temporal and frontal - Small GM volume in the hippocampus,
lobes, precuneus, cerebellum and the amygdala and the prefrontal, frontal,
thalami regions parietal and occipital lobes.
- increased connectivity in coupling of -Lower connectivity in the coupling of
social salience-ventral medial prefrontal social salience-right fronto-parietal
cortex and default mode networks
precuneus networks

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Massó Rodriguez et al.
to differentiate BPD from BD-I, the difference between BPD and
BD-II is much more challenging and often confusing in clinical
settings. Especially in cases of a pronounced affective instability
or rapid cycling (four or more affective episodes a year), both
conditions present with the aforementioned affective symptoms.
An important neurobiological underpinning might hereby be the
underlying abnormal temperamental traits, which are considered
as genetically stable and are hypothesized as etiological risk
factors for both BPD and BD (29). We found evidence that BD-II
and BPD share higher scores in all affective temperamental traits,
with a greater severity in cyclothymic, depressive, irritable and
anxious temperaments in patients with BPD and, conversely, the
hyperthymic temperament being more specific to BD. Akiskal (9)
hypothesized hereby that BPD belongs to the affective spectrum
as “the dysphoric facet of cyclothymia” due to the extreme
emotional reactivity in BPD, which is based on abnormal affective
temperament and cyclothymia (with brief alternating hypomanic
and depressive symptoms) in both disorders.
Childhood trauma, such as emotional abuse and neglect,
is associated with both BPD and BD and, specifically,
with emotional regulation difficulties and propensity to
impulsiveness (38, 72, 73). While both patient groups had
significantly experienced trauma, results point to the severity
of abuse being more marked in BPD patients. In our review,
preliminary neuroimaging evidence shows that BPD and BD
share overlapping functional and structural neuroanatomical
abnormalities, especially involving temporal lobe and related
limbic structures associated with mood lability and rapid
cycling. These abnormalities could be associated with childhood
maltreatment and, in turn, with high sensitivity to rejection,
and with impulsiveness, all characteristic factors of both BPD
(38, 66, 72, 73) and BD (49, 61, 66, 73, 74). Based on these
results, impulsivity could be conceptualized as a consequence
of malfunctioning emotion regulation mechanisms or even as a
facet of emotional dysregulation, rather than an expression of
impulsivity as a primary trait. However, results diverge here as
well. Plasma cortisol levels and sexual abuse were correlated in
both diagnostic-related groups, but in opposite ways. In BPD,
the level of cortisol was positively correlated with sexual abuse,
while in BD the correlation was negative. Thus, in BPD patients
the history of sexual abuse could stimulate the functioning of
the HPA axis while in BD patients a more inhibitory response
is observed. Additionally, a negative correlation was identified
between emotional neglect and physical neglect, and plasma
cortisol levels in BPD patients.
These results highlight the need to research further the
role of childhood trauma in the nosology of these disorders
and are in line with the previous data on the etiology of
these disorders. Recent reviews suggest that BD could be the
result of a gene x environment interaction, supporting the
evidence from this review that environmental factors such as
childhood trauma and adverse life events play a significant
role (75–77), while a recent review by Cattane et al. (61)
suggests that BPD is a result of a combination of biological
vulnerabilities and environmental factors including the exposure
to traumatic experiences during childhood. Early life stress and
childhood trauma have been seen to be major risk factors
for the development and persistence of BPD, contributing to
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Borderline Personality Disorder Bipolar Disorder
the emergence of hippocampal abnormalities. In this sense,
the subiculum modulates the response to stress, influencing
the hypothalamic-pituitary-adrenal (HPA) axis and being the
primary locus of hippocampal interaction with this axis (61). On
the other hand, atrophy in the dentate gyrus is associated with
deficits in the GABAergic system which have been implicated
in the etiology of BD (46). Additionally, the impairment in
the former network was related to deficits in conscious self-
representation and in turn with impaired social understanding,
while impairment in the second network explained emotional
clarity deficits and depressive rumination (48). In this line,
these results could explain why bipolar patients have heightened
awareness and increased sensitivity and receptivity to social
inputs, but because of diminished emotional clarity, they are
unable to process the meaning of these inputs with respect to
internal emotional milieu. Nevertheless, few studies have been
carried out in this direction, so the results must be interpreted
with caution and are not robust enough to draw firm conclusions.
Greater understanding of the etiology of the two disorders in
the future may help answer our research question, especially
in light of the fact that debate over the clinical similarities
and differences has gone on for a long time without a decisive
consensus being reached.
Other variables should be also mentioned here, even though
they have not been targeted in this review. One is longitudinal
data. A review by Parker (17) regarding whether BPD can
be classified as a mood disorder argues that longitudinal data
helps clarify the distinction between BPD and BD-II. On
the other hand, a recent article suggests the course of BPD
frequently changes over time, with symptoms fluctuating to
such an extent that they no longer fulfill the diagnostic criteria
later in the life course (78), unlike BD which tends to be a
lifelong disorder. As Diagnostic and Statistical Manual of Mental
Disorders (DSM) criteria state that traits in personality disorders
are chronic and pervasive (63), this puts into doubts the nature
of BPD as a personality disorder, and could be considered as a
further argument for summarizing BPD within a broad affective
spectrum with a shift from an Axis II to Axis I disorder. In our
review, all the studies which met the inclusion criteria were cross-
sectional, and it would be interesting to see longitudinal research
directly comparing the two disorders.
Furthermore, pharmacological treatment and psychotherapy
in BPD is worth mentioning due to the nosological nature of
our review and its frequent use in clinical practice. Ghaemi
et al. (3) argue certain treatment effects may be diagnostically
specific. They support there being a strong consensus that
psychotherapies alone are not effective in BD but they may
be effective adjunctively with medications while, in contrast,
psychotherapy is central to the treatment for BPD and there
exists controversy about the benefits of psychopharmacotherapy
(3). As well, a recent review of pharmacological treatment and
psychotherapy in BPD recommends in general terms the use of
both strategies (79). The authors highlight the need for further
large randomized controlled pharmacological trials across classes
of medication (especially in antidepressants) in BPD, but state
that the available evidence suggests that anticonvulsants (mainly
valproate and lamotrigine), atypical antipsychotics (especially
olanzapine) are therapeutic options in treating impulsivity, anger,
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Massó Rodriguez et al.
and affective instability in BPD patients. All these agents are
indicated and frequently used in BD. This is of interest as core
symptoms of both BPD and BD disorders can improve with
medication (80).
However, the different psychotherapeutic treatment options
appear to favor a more dichotomous approach to both
conditions. The disorders differ in terms of the triggers of
mood change. In BPD, most of the mood swings are associated
with interpersonal triggers, while in BD they are related more
often to biological factors linked to sleeping habits, self-care
and changes of season. Thus, BD psychotherapy would address
risk factors and environmental triggers to reduce emotional
dysregulation (81) while BPD psychotherapy would be focused
on social coping and trouble resolution strategies in the form
of Dialectic Behavior Therapy (DBT) to improve emotional
regulation (82). This would again support the idea that in
BPD, the mood tends to change over time and in response to
interpersonal conflict, whereas in BD the change lasts for a few
days and the triggers are less clear. On the other hand, and based
on the similarities observed in cognitive performance in both
conditions, some studies have included cognitive rehabilitation
and cognitive remediation techniques in their intervention. A
systematic review carried out by Bellani et al. (83) states that
there is evidence of functional and cognitive improvements in
patients with BD who have undergone cognitive remediation
treatment. Pascual et al. (84) carried out a controlled study of
cognitive rehabilitation in patients with BPD, observing also an
improvement in the psychosocial functioning of these patients.
These results have led the authors to propose the possible
efficacy of broader interventions which might help both disorders
and include the elements of the psychoeducational model,
DBT emotional regulation techniques and, in turn, cognitive
remediation strategies.
Strengths of this work include that this is, to the best of our
knowledge, the first systematic review that involves only studies
which directly compare both disorders and review clinical and
neuropsychological features and neuroimaging data. Due to the
comparative lack of data of these last two categories, most of the
discussion focuses on the clinical features. This review comprises
a total sample of 2,631 participants which provides interesting
preliminary evidence and directions for future research. Another
strength of the review was the search of three databases for
articles over an extended timeframe, repeated by an independent
reviewer with a third to resolve discrepancies.
Limitations of our work need to be taken into account and
include a lack of longitudinal studies and that several studies
had no HC group, meaning an estimation of the degree of
impairment or clinical severity of the patients is difficult. Several
studies did not confirm the diagnosis of one or both clinical
groups or confirm the lack of psychopathology in the control
group. Additionally, studies differed in how the BD group was
defined, with the majority not distinguishing between BD-I and
BD-II in the statistical analysis, while others focused on BD-
II or cyclothymia, making generalizations difficult, as well as
differences in whether BD samples were euthymic or in an
acute phase. Many studies did not compare BD and BPD during
depressive episodes, when there are many overlapping symptoms
(85). Three studies did not confirm diagnosis as part of the study
Frontiers in Psychiatry | www.frontiersin.org
Borderline Personality Disorder Bipolar Disorder
(24, 26, 37), while four studies did not screen the control group
for psychopathology (23, 31, 46, 47). There could have been
comorbidity or a BD/BPD diagnosis in these groups which would
have confounded results. A large variety of diagnostic tools and
measures and scales were employed between the studies. Some
studies relied on self-report measures for some or all outcome
variables. All childhood maltreatment data was retrospective and
self-report, meaning they may be subject to recall bias and an
individual’s subjective interpretation of events (86), which may
have limited validity (87). Pharmacological treatment, the first-
line treatment for BD and often used to stabilize mood in BPD
(71), may have confounded results and was controlled for only in
a minority of studies. Additionally, some studies used only female
samples, meaning findings may not be generalizable to males. As
well, two studies (19, 35) appeared to use the same sample, as
did the group of Saunders et al. (44, 45) and the group of Rossi
et al. (46, 47), meaning findings may be distorted. Finally, only
three imaging studies are included in the review. One study (48)
was performed with fMRI at resting state in a sample of 16 BD
patients and 14 BPD, and two studies by almost the same authors
(46, 47) were performed with sMRI in the same small sample
of patients and controls. The sample size for significance of
both functional and structural studies was not reached, meaning
these studies were underpowered, thus the conclusions of these
studies cannot be generalized to the general population of BD and
BDP patients.
CONCLUSION
In conclusion, based on current evidence directly comparing the
two disorders, there is not sufficient data to either confirm the
distinction as separate nosological entities, or to support both
disorders being part of a shared affective spectrum continuum,
or BPD being a bipolar sub-type. Although the results obtained in
this exhaustive review may lead us to support the view of BD and
BPD as two different categories, in clinical practice the differences
between both are often very subtle, especially between BD-II and
BPD. leading us to contemplate a dimensional vision.
Common criteria such as emotional dysregulation are easily
identified but focusing on differential symptoms is a more
complex task. BD-I differs clearly from BPD in the sense of
manic/mixed phases which require hospitalization and affective
instability has different pathways, being especially common
interpersonal triggers in BPD. Furthermore, impulsivity
seems more a trait in BPD, whereas a state in BD, and
decreases over time in BPD, unlike in BD, supported by
some neuropsychological findings. On the other hand, most
symptoms, especially depressive, anxious, and hypomanic mixed
symptoms are shared in both conditions (with a greater emphasis
on BD-II than BD-I), even though they may be more intense in
BPD. The latter might indicate that BPD is on the upper end
of the affective spectrum as a temporal (as diagnosis of BPD
changes over time), but more severe condition, whereas BD
tends to be a lifelong disorder. Central shared parts of both
conditions are affective temperament, even though some are
more specific for one or the other entity, and adverse experiences
in childhood, which have an especially important etiological role
that is objectified in structural and functional brain alterations,
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Massó Rodriguez et al.
which can explain symptomatic deficits. The noxious sense of self
and difficulties in interpersonal relationships are characteristic
of BPD. Neuropsychological, but especially neuroimaging, data
are inconclusive so far to decide on the nosological discussion
between both disorders. However, a recent Genome Wide
Association Study by Witt and colleagues (88) revealed that
“rather than being a discrete entity,” BPD has an etiological
overlap with major psychosis, including BD. We must not forget
other factors that can help us in the distinction as the family
history of BD, the incidence of suicide and suicide attempts, the
pharmacology response, the form of mood cycling or psychotic
episodes or the incidence of early sexual abuse.
Future lines of investigation should focus on clinical and
neuobiological variables with larger samples and hetero-applied
scales, translating this information into effective diagnostic
tests and treatment techniques for both disorders. It would
be necessary to carry out more clinical trials focused mainly
on neuropsychological and neuroimaging aspects directly
comparing BD and BPD to increase the understanding
of common and differentiated aspects between these two
clinical conditions. In particular, prospective, longitudinal cross-
diagnostic studies are needed to clarify the controversy. Some
authors advocate for a multivariate approach that goes beyond
the categorical distinction and uses dimensional information
as a better way to understand the relationship between BPD
and BD-II (89). Current diagnostic systems demonstrate a
move toward dimensional rather than categorical approaches
to classifying personality pathology and specially to consider
personality traits in the management of all patients with
BD irrespective of whether criteria for a categorical BPD
are met (90). In this line, the alternative model proposed
by the 5th edition of Diagnostic and Statistical Manual of
Mental Disorders (63) and the 11th edition of International
Classification of Diseases for Mortality and Morbidity Statistics
(91) point to dimensions in BPD. Thus, another approach would
investigate personality disorder dimensions in the BD spectrum.
DATA AVAILABILITY STATEMENT
The original contributions presented in the study
are included in the article/Supplementary Material,
REFERENCES
1. Fornaro M, Orsolini L, Marini S, De Berardis D, Perna G, Valchera A, et al.
The prevalence and predictors of bipolar and borderline personality disorders
comorbidity: systematic review and meta-analysis. J Affect Disord. (2016)
195:105–18. doi: 10.1016/j.jad.2016.01.040
2. Benazzi F. Does temperamental instability support a continuity between
bipolar II disorder and major depressive disorder? Eur Psychiatry. (2006)
21:274–9. doi: 10.1016/j.eurpsy.2006.02.003
3. Ghaemi SN, Dalley S, Catania C, Barroilhet S. Bipolar or borderline: a
clinical overview. Acta Psychiatr Scand. (2014) 130:99–108. doi: 10.1111/acps.
12257
Frontiers in Psychiatry | www.frontiersin.org
Borderline Personality Disorder Bipolar Disorder
further inquiries can be directed to the
corresponding author/s.
AUTHOR CONTRIBUTIONS
AM and BH separately carried out the search and the primary
assessment of the quality of non-randomized studies and wrote
the first draft of the manuscript, supervised by AM-A. Two
researchers, IG-S and AV-G, resolved discrepancies. AM-A,
BA, VP, FC, FP, and DM, experts within the investigated
field and contributed with the interpretation of data. AG-
E and AT participated with contributions to the manuscript.
All authors contributed to the article and approved the
submitted version.
FUNDING
BA receives two grants (PI/15/02242 and PI18/00009) from the
Instituto de Salud Carlos III-Subdirección General de Evaluación
y Fomento de la Investigación, Plan Nacional 2008–2011 and
2013–2016, a NARSARD Independent Investigator Grant from
the Brain & Behavior Research Foundation (24397) and a grant
within the Pla estratègic de recerca i innovació en salut (PERIS;
G60072253) by the Catalan Government. He acknowledges
also the continuous support by the CIBERSAM (Centro de
Investigación Biomédica en Red de Salud Mental). BH thanks the
support and funding of the Instituto de Salud Carlos III through
a PFIS grant (FI10/00017). FC thanks the support and funding of
the Spanish Ministry of Economy and Competitiveness, through
a FIS (PI15/00588; PI19/00009), and the Secretaria d’Universitats
i Recerca del Departament d’Economia i Coneixement de la
Generalitat de Catalunya GOVERNMENT OF CATALONIA
(2017_SGR_134). The funding institutions had no role in the
study design, data collection and analysis, decision to publish, or
preparation of the manuscript.
SUPPLEMENTARY MATERIAL
The Supplementary Material for this article can be found
online at: https://www.frontiersin.org/articles/10.3389/fpsyt.
2021.681876/full#supplementary-material
4. Gunderson JG, Phillips KA. A current view of the interface between borderline
personality disorder and depression. Am J Psychiatry. (1991) 148:967–
75. doi: 10.1176/ajp.148.8.967
5. Brieger P, Ehrt U, Marneros A. Frequency of comorbid personality disorders
in bipolar and unipolar affective disorders. Compr Psychiatry. (2003) 44:28–
34. doi: 10.1053/comp.2003.50009
6. Paris J, Gunderson J, Weinberg I. The interface between borderline personality
disorder and bipolar spectrum disorders. Compr Psychiatry. (2007) 48:145–54.
doi: 10.1016/j.comppsych.2006.10.001
7. Fan AH, Hassell J. Bipolar disorder and comorbid personality
psychopathology: a review of the literature. J Clin Psychiatry. (2008)
69:1794–803. doi: 10.4088/JCP.v69n1115
15 June 2021 | Volume 12 | Article 681876
Massó Rodriguez et al.
8. Zimmerman M, Morgan TA. Problematic boundaries in the diagnosis of
bipolar disorder: the interface with borderline personality disorder. Curr
Psychiatry Rep. (2013) 15:422. doi: 10.1007/s11920-013-0422-z
9. Akiskal HSS. Demystifying borderline personality: critique of the concept and
unorthodox reflections on its natural kinship with the bipolar spectrum. Acta
Psychiatr Scand. (2004) 110:401–7. doi: 10.1111/j.1600-0447.2004.00461.x
10. Benazzi F. Borderline personality-bipolar spectrum relationship.
Prog Neuropsychopharmacol Biol Psychiatry. (2006) 30:68–
74. doi: 10.1016/j.pnpbp.2005.06.010
11. Deltito J, Martin L, Riefkohl J, Austria B, Kissilenko A, Corless P, et al. Do
patients with borderline personality disorder belong to the bipolar spectrum?
J Affect Disord. (2001) 67:221–8. doi: 10.1016/S0165-0327(01)00436-0
12. Perugi G, Toni C, Travierso MC, Akiskal HS. The role of cylothymia
in atypical depression: toward a data-based reconceptualization
of the borderline-bipolar II connection. J Affect Disord. (2003)
73:87–98. doi: 10.1016/S0165-0327(02)00329-4
13. Zimmerman M, Ruggero CJ, Chelminski I, Young D. Psychiatric diagnoses
in patients previously overdiagnosed with bipolar disorder. J Clin Psychiatry.
(2010) 71:26–31. doi: 10.4088/JCP.08m04633
14. Paris J. Differential diagnosis of borderline personality disorder. Psychiatr Clin
North Am. (2018) 41:575–82. doi: 10.1016/j.psc.2018.07.001
15. Magill CA. The boundary between borderline personality disorder and bipolar
disorder: current concepts and challenges. Can J Psychiatry. (2004) 49:551–
6. doi: 10.1177/070674370404900806
16. Basset D. Borderline personality disorder and bipolar affective disorder.
Spectra o spectre? A review. Aust N Z J Psichiatry. (2012) 46 327–
39. doi: 10.1177/0004867411435289
17. Parker G. Is borderline personality disorder a mood disorder? Br J Psychiatry.
(2014) 204:252–3. doi: 10.1192/bjp.bp.113.136580
18. Sanches M. The limits between bipolar disorder and borderline
personality disorder: a review of the evidence. Diseases. (2019)
7:49. doi: 10.3390/diseases7030049
19. Bayes AJ, McClure G, Fletcher K, Román Ruiz del Moral YE, Hadzi-
Pavlovic D, Stevenson JL, et al. Differentiating the bipolar disorders from
borderline personality disorder. Acta Psychiatr Scand. (2016) 133:187–
95. doi: 10.1111/acps.12509
20. Moher D, Liberati A, Tetzlaff J, Altman DG, PRISMA Group. Preferred
reporting items for systematic reviews and meta-analyses: the PRISMA
statement. BMJ. (2009) 339:b2535. doi: 10.1136/bmj.b2535
21. Ryan R, Cochrane Consumers and Communication Review Group. Cochrane
Consumers and Communication Review Group: Data Synthesis and Analysis.
(2013). Available online at: http://cccrg.cochrane.org (accessed May, 2021).
22. Wells G, Shea B, O’Connell D, Peterson J, Welch V, Losos M, et al. The
Newcastle-Ottawa Scale (NOS) for Assessing the Quality of Nonrandomised
Studies in Meta-Analysis. (2011). Available online at: http://www.ohri.ca/
programs/clinical_epidemiology/oxford.asp (accessed May, 2021).
23. Berrocal C, M RM, Rando MA, Benvenuti A, Cassano GB. Borderline
personality disorder and mood spectrum. Psychiatry Res. (2008) 159:300–
7. doi: 10.1016/j.psychres.2007.10.002
24. Pauselli L, Verdolini N, Santucci A, Moretti P, Quartesan R. Bipolar
and borderline personality disorders: a descriptive comparison of
psychopathological aspects in patients discharged from an Italian Inpatient
Unit using PANSS and BPRS. Psychiatr Danub. (2015) 27(Suppl. 1):S170−6.
25. Vöhringer PA, Barroilhet SA, Alvear K, Medina S, Espinosa C, Alexandrovich
K, et al. The International Mood Network (IMN) Nosology Project:
differentiating borderline personality from bipolar illness. Acta Psychiatr
Scand. (2016) 134:504–10. doi: 10.1111/acps.12643
26. di Giacomo E, Aspesi F, Fotiadou M, Arntz A, Aguglia E, Barone L, et al.
Unblending borderline personality and bipolar disorders. J Psychiatr Res.
(2017) 91:90–7. doi: 10.1016/j.jpsychires.2017.03.006
27. Perroud N, Zewdie S, Stenz L, Adouan W, Bavamian S, Prada P, et al.
Methylation of serotonin receptor 3A in ADHD, borderline personality,
and bipolar disorders: link with severity of the disorders and childhood
maltreatment. Depress Anxiety. (2016) 33:45–55. doi: 10.1002/da.22406
28. Saunders KEA, Goodwin GM, Rogers RD. Borderline personality disorder, but
not euthymic bipolar disorder, is associated with a failure to sustain reciprocal
cooperative behaviour: implications for spectrum models of mood disorders.
Psychol Med. (2015) 45:1591–600. doi: 10.1017/S0033291714002475
Frontiers in Psychiatry | www.frontiersin.org
Borderline Personality Disorder Bipolar Disorder
29. Bachetti MC, Brufani F, Spollon G, Moretti P. Dysphoria dimensions: a
preliminary inpatients study to diffrentiate borderline personality and bipolar
disorder spectrum. Psychiatr Danub. (2019) 31(Suppl. 3):490–6.
30. Eich D, Gamma A, Malti T, Vogt Wehrli M, Liebrenz M, Seifritz E,
et al. Temperamental differences between bipolar disorder, borderline
personality disorder, and attention deficit/hyperactivity disorder: some
implications for their diagnostic validity. J Affect Disord. (2014) 169:101–
4. doi: 10.1016/j.jad.2014.05.028
31. Nilsson AKK, Jorgensen CR, Straarup KN, Licht RW. Severity of
affective temperament and maladaptive self-schemas differentiate borderline
patients, bipolar patients, and controls. Compr Psychiatry. (2010) 51:486–91.
doi: 10.1016/j.comppsych.2010.02.006
32. Mneimne M, Fleeson W, Arnold EM, Furr RM. Differentiating the everyday
emotion dynamics of borderline personality disorder from major depressive
disorder and bipolar disorder. Person Disord Theory Res Treat. (2017) 9:192–6.
doi: 10.1037/per0000255
33. Henry C, Mitropoulou V, New A, Koenigsberg H, Silverman J, Siever L.
Affective instability and impulsivity in borderline personality and bipolar
II disorders: similarities and differences. J Psychiatr Res. (2001) 35:307–
12. doi: 10.1016/S0022-3956(01)00038-3
34. Reich DB, Zanarini MC, Fitzmaurice G. Affective lability in bipolar disorder
and borderline personality disorder. Compr Psychiatry. (2012) 53:230–
7. doi: 10.1016/j.comppsych.2011.04.003
35. Bayes A, Parker G, McClure G. Emotional dysregulation in those with bipolar
disorder, borderline personality disorder and their comorbid expression. J
Affect Disord. (2016) 204:103–11. doi: 10.1016/j.jad.2016.06.027
36. Fletcher K, Parker G, Bayes A, Paterson A, McClure G. Emotion regulation
strategies in bipolar II disorder and borderline personality disorder:
differences and relationships with perceived parental style. J Affect Disord.
(2014) 157:52–9. doi: 10.1016/j.jad.2014.01.001
37. Kramer U. Observer-rated coping associated with borderline personality
disorder: an exploratory study. Clin Psychol Psychother. (2014) 21:242–
51. doi: 10.1002/cpp.1832
38. Richard-Lepouriel H, Kung AL, Hasler R, Bellivier F, Prada P, Gard
S, et al. Impulsivity and its association with childhood trauma
experiences across bipolar disorder, attention deficit hyperactivity
disorder and borderline personality disorder. J Affect Disord. (2019)
244:33–41. doi: 10.1016/j.jad.2018.07.060
39. Mazer AK, Cleare AJ, Young AH, Juruena MF. Bipolar affective disorder
and borderline personality disorder: differentiation based on the history of
early life stress and psychoneuroendocrine measures. Behav Brain Res. (2019)
357–8:48–56. doi: 10.1016/j.bbr.2018.04.015
40. Akbari V, Rahmatinejad P, Mohammadi SD. Comparing neurocognitive
profile of patients with borderline personality and bipolar–II disorders. Iran
J Psychiatry. (2019) 14:113. doi: 10.18502/ijps.v14i2.990
41. Feliu-Soler A, Soler J, Elices M, Pascual JC, Perez J, Martin-Blanco
A, et al. Differences in attention and impulsivity between borderline
personality disorder and bipolar disorder. Psychiatry Res. (2013) 210:1307–
9. doi: 10.1016/j.psychres.2013.09.011
42. Gvirts HZ, Braw Y, Harari H, Lozin M, Boche Y, Fefer K, et al. Executive
dysfunction in bipolar disorder and borderline personality disorder. Eur
Psychiatry. (2015) 30:959–64. doi: 10.1016/j.eurpsy.2014.12.009
43. Lozano V, Soriano MF, Aznarte JI, Gomez-Ariza CJ, Bajo MT. Interference
control commonalities in patients with schizophrenia, bipolar disorder, and
borderline personality disorder. J Clin Exp Neuropsychol. (2016) 38:238–
50. doi: 10.1080/13803395.2015.1102870
44. Saunders KEA, Goodwin GM, Rogers RD. Borderline personality disorder,
but not euthymic bipolar I disorder, is associated with prolonged post-
error slowing in sensorimotor performance. J Affect Disord. (2016) 198:163–
70. doi: 10.1016/j.jad.2016.03.027
45. Saunders KEA, Goodwin GM, Rogers RD. Insensitivity to the magnitude of
potential gains or losses when making risky choices: women with borderline
personality disorder compared with bipolar disorder and controls. J Pers
Disord. (2016) 30:530–44. doi: 10.1521/pedi_2015_29_216
46. Rossi R, Lanfredi M, Pievani M, Boccardi M, Beneduce R, Rillosi L, et al.
Volumetric and topographic differences in hippocampal subdivisions in
borderline personality and bipolar disorders. Psychiatry Res Neuroimaging.
(2012) 203:132–8. doi: 10.1016/j.pscychresns.2011.12.004
16 June 2021 | Volume 12 | Article 681876
Massó Rodriguez et al.
47. Rossi R, Pievani M, Lorenzi M, Boccardi M, Beneduce R,
Bignotti S, et al. Structural brain features of borderline personality
and bipolar disorders. Psychiatry Res Neuroimaging. (2013)
213:83–91. doi: 10.1016/j.pscychresns.2012.07.002
48. Das P, Calhoun V, Malhi GS. Bipolar and borderline patients display
differential patterns of functional connectivity among resting state networks.
Neuroimage. (2014) 98:73–81. doi: 10.1016/j.neuroimage.2014.04.062
49. Bøen E, Hummelen B, Elvsåshagen T, Boye B, Andersson S, Karterud S, et al.
Different impulsivity profiles in borderline personality disorder and bipolar II
disorder. J Affect Disord. (2015) 170:104–11. doi: 10.1016/j.jad.2014.08.033
50. Akiskal HS. The temperamental foundations of affective disorders. In: Mundt
C, Goldstein MJ, Hahlweg K, Fiedler P, editors. Interpersonal Factors in the
Origin and Course of Affective Disorders. London: Gaskill (1996). p. 3–30.
51. Romero E, Holtzman JN, Tannenhaus L, Monchablon R, Rago CM, Lolich
M, et al. Neuropsychological performance and affective temperaments in
Euthymic patients with bipolar disorder type II. Psychiatry Res. (2016)
238:172–80. doi: 10.1016/j.psychres.2016.02.032
52. Vázquez GH, Baldessarini RJ, Tondo L. Co-occurrence of anxiety and bipolar
disorders: clinical and therapeutic overview. Depress Anxiety. (2014) 31:196–
206. doi: 10.1002/da.22248
53. Thompson RA. Emotion dysregulation: a theme in search of definition. Dev
Psychopathol. (2019) 31:805–15. doi: 10.1017/S0954579419000282
54. Beauchaine TP. Future directions in emotion dysregulation and
youth psychopathology. J Clin Child Adolesc Psychol. (2015)
44:875–96. doi: 10.1080/15374416.2015.1038827
55. Broome MR, He Z, Iftikhar M, Eyden J, Marwaha S. Neurobiological
and behavioural studies of affective instability in clinical
populations: a systematic review. Neurosci Biobehav Rev. (2015)
51:243–54. doi: 10.1016/j.neubiorev.2015.01.021
56. Coifman KG, Berenson KR, Rafaeli E, Downey G. From negative to
positive and back again: polarized affective and relational experience
in borderline personality disorder. J Abnorm Psychol. (2012) 121:668–
79. doi: 10.1037/a0028502
57. Tsanas A, Saunders KEAEA, Bilderbeck ACC, et al. Daily longitudinal self-
monitoring of mood variability in bipolar disorder and borderline personality
disorder. J Affect Disord. (2016) 205:225–33. doi: 10.1016/j.jad.2016.06.065
58. Wessa M, Linke J. Emotional processing in bipolar disorder:
behavioural and neuroimaging findings. Int Rev Psychiatry. (2009)
21:357–67. doi: 10.1080/09540260902962156
59. VandenBos GR, (editor). APA Dictionary of Psychology. Washington, DC:
American Psychological Association (2007).
60. Aas M, Henry C, Andreassen OA, Bellivier F, Melle I, Etain B. The role
of childhood trauma in bipolar disorders. Int J Bipolar Disord. (2016) 4:1–
10. doi: 10.1186/s40345-015-0042-0
61. Cattane N, Rossi R, Lanfredi M, Cattaneo A. Borderline personality
disorder and childhood trauma: exploring the affected biological systems and
mechanisms. BMC Psychiatry. (2017) 17:221. doi: 10.1186/s12888-017-1383-2
62. Bayes A, Parker G, Paris J. Differential diagnosis of bipolar II disorder
and borderline personality disorder. Curr Psychiatry Rep. (2019) 21:1–
11. doi: 10.1007/s11920-019-1120-2
63. American Psychiatric Association. Diagnostic and Statistical Manual of Mental
Disorders. 5th ed. Arlington, VA (2013).
64. Lewis M, Scott J, Frangou S. Impulsivity, personality and bipolar disorder. Eur
Psychiatry. (2009) 24:464–9. doi: 10.1016/j.eurpsy.2009.03.004
65. Swann AC, Steinberg JL, Lijffijt M, Moeller FG. Impulsivity: differential
relationship to depression and mania in bipolar disorder. J Affect Disord.
(2008) 106:241–8. doi: 10.1016/j.jad.2007.07.011
66. Etain B, Aas M, Andreassen OA, Lorentzen S, Dieset I, Gard S, et al. Childhood
trauma is associated with severe clinical characteristics of bipolar disorders. J
Clin Psychiatry. (2013) 74:991–8. doi: 10.4088/JCP.13m08353
67. Oquendo MA, Perez-Rodriguez MM, Poh E, Sullivan G, Burke AK,
Sublette ME, et al. Life events: a complex role in the timing of
suicidal behavior among depressed patients. Mol Psychiatry. (2014) 19:902–
9. doi: 10.1038/mp.2013.128
68. Goodwin F Jamison K. Manic-depressive Illness: Bipolar Disorders and
Recurrent Depression. 2nd ed. New York, NY: Oxford University Press (2007).
p. 411–62.
Frontiers in Psychiatry | www.frontiersin.org
Borderline Personality Disorder Bipolar Disorder
69. Torgersen S, Lygren S, Oien PA, SkrE I, Onstad S, Edvardsen J, et al.
A twin study of personality disorders. Compr Psychiatry. (2000) 41:416–
25. doi: 10.1053/comp.2000.16560
70. Torgersen S, Czajkowski N, Jacobson K, Reichborn-Kjennerud T, Røysamb E,
Neale MC, et al. Dimensional representations of DSM-IV cluster B personality
disorders in a population-based sample of Norwegian twins: a multivari-
ate study. Psychol Med. (2008) 38:1617–25. doi: 10.1017/S00332917080
02924
71. Goodwin GM. Evidence-based guidelines for treating bipolar
disorder: revised second edition-recommendations from the British
association for psychopharmacology. J Psychopharmacol. (2009)
23:346–88. doi: 10.1177/0269881109102919
72. Foxhall M, Hamilton-Giachritsis C, Button K. The link between rejection
sensitivity and borderline personality disorder: a systematic review and
meta-analysis. Br J Clin Psychol. (2019) 58:289–326. doi: 10.1111/bjc.
12216
73. Alloy LB, Abramson LY, Walshaw PD, Neeren AM. Cognitive vulnerability
to unipolar and bipolar mood disorders. J Soc Clin Psychol. (2006) 25:726–
54. doi: 10.1521/jscp.2006.25.7.726
74. Leverich GS, McElroy SL, Suppes T, Keck PE, Denicoff KD,
Nolen WA, et al. Early physical and sexual abuse associated
with an adverse course of bipolar illness. Biol Psychiatry. (2002)
51:288–97. doi: 10.1016/S0006-3223(01)01239-2
75. Jansen K, Cardoso TA, Fries GR, Branco JC, Silva RA, Kauer-Sant’Anna
M, et al. Childhood trauma, family history, and their association with
mood disorders in early adulthood. Acta Psychiatr Scand. (2016) 134:281–
6. doi: 10.1111/acps.12551
76. Misiak B, Stramecki F, Gaweda Ł, Prochwicz K, Sasiadek MM, Moustafa AA,
et al. Interactions between variation in candidate genes and environmental
factors in the etiology of schizophrenia and bipolar disorder: a systematic
review. Mol Neurobol. (2018) 55:5075–100. doi: 10.1007/s12035-017-
0708-y
77. Bortolato B, Köhler CA, Evangelou E, León-Caballero J, Solmi M, Stubbs B,
et al. Systematic assessment of environmental risk factors for bipolar disorder:
an umbrella review of systematic reviews and meta-analyses. Bipolar Disord.
(2017) 19:84–96. doi: 10.1111/bdi.12490
78. Temes CM, Zanarini MC. The longitudinal course of borderline
personality disorder. Psychiatr Clin North Am. (2018) 41:685–
94. doi: 10.1016/j.psc.2018.07.002
79. Bozzatello P, Rocca P, De Rosa ML, Bellino S. Current and
emerging medications for borderline personality disorder: is
pharmacotherapy alone enough? Exp Opin Pharmacother. (2020)
21:47–61. doi: 10.1080/14656566.2019.1686482
80. Crawford MJ, MacLaren T, Reilly JG. Are mood stabilisers helpful in
treatment of borderline personality disorder? BMJ. (2014) 349:g5378.
doi: 10.1136/bmj.g5378
81. Colom F, Vieta E. A perspective on the use of psychoeducation, cognitive-
behavioral therapy and interpersonal therapy for bipolar patients. Bipolar
Disord. (2004) 6:480–6. doi: 10.1111/j.1399-5618.2004.00136.x
82. Linehan MM. Cognitive Behavioural Treatment of Borderline Personality
Disorder. New York, NY: Guildford Press (1993).
83. Bellani M, Biagianti B, Zovetti N, Rossetti MG, Bressi C, Perlini C, et al.
The effects of cognitive remediation on cognitive abilities and real-world
functioning among people with bipolar disorder: a systematic review. J Affect
Disord. (2019) 257:691–7. doi: 10.1016/j.jad.2019.07.059
84. Pascual JC, Palomares N, Ibáñez Á, Portella MJ, Arza R, Reyes R, et al.
Efficacy of cognitive rehabilitation on psychosocial functioning in borderline
personality disorder: a randomized controlled trial. BMC Psychiatry. (2015)
15:255. doi: 10.1186/s12888-015-0640-5
85. Socada JL, Söderholm JJ, Rosenström T, Ekelund J, Isometsä E.
Presence and overlap of bipolar symptoms and borderline features
during major depressive episodes. J Affect Disord. (2021) 280 (Pt
A):467–77. doi: 10.1016/j.jad.2020.11.043
86. Frissa S, Hatch SL, Fear NT, Dorrington S, Goodwin L, Hotopf M. Challenges
in the retrospective assessment of trauma: comparing a checklist approach to
a single item trauma experience screening question. BMC Psychiatry. (2016)
16:20. doi: 10.1186/s12888-016-0720-1
17 June 2021 | Volume 12 | Article 681876
Massó Rodriguez et al.
87. Danese A, Widom CS. Objective and subjective experiences of child
maltreatment and their relationships with psychopathology. Nat Hum Behav.
(2020) 4:811–8. doi: 10.1038/s41562-020-0880-3
88. Witt SH, Streit F, Jungkunz M, Frank J, Awasthi S, Reinbold CS, et al.
Genome-wide association study of borderline personality disorder reveals
genetic overlap with bipolar disorder, major depression and schizophrenia.
Transl Psychiatry. (2017) 7:e1155. doi: 10.1038/tp.2017.115
89. Villarroel J, Salinas V, Silva H, Herrera L, Montes C, Jerez S, et al. Beyond the
categorical distinction between borderline personality disorder and bipolar
ii disorder through the identification of personality traits profiles. Front
Psychiatry. (2020) 11:552. doi: 10.3389/fpsyt.2020.00552
90. Saunders KEA, Jones T, Perry A, Di Florio A, Craddock N, Jones I, et al.
The influence of borderline personality traits on clinical outcomes in bipolar
disorder. Bipolar Disord. (2020). doi: 10.1111/bdi.12978. [Epub ahead of
print].
91. World Health Organization. International Classification of Diseases for
Mortality and Morbidity Statistics. 11th Revision. (2018). Available online
at: https://icd.who.int/browse11/l-m/en (accessed May, 2021).
Frontiers in Psychiatry | www.frontiersin.org
Borderline Personality Disorder Bipolar Disorder
Conflict of Interest: FP is a member of the European Scientific Advisory Board
of Brainsway Inc., Jerusalem, Israel, and has received speaker’s honoraria from
Mag & More GmbH and the neuroCare Group. His lab has received support with
equipment from neuroConn, Ilmenau, Germany, and Mag & More GmbH and
Brainsway Inc., Jerusalem, Israel.
The remaining authors declare that the research was conducted in the absence of
any commercial or financial relationships that could be construed as a potential
conflict of interest.
Copyright © 2021 Massó Rodriguez, Hogg, Gardoki-Souto, Valiente-Gómez, Trabsa,
Mosquera, García-Estela, Colom, Pérez, Padberg, Moreno-Alcázar and Amann. This
is an open-access article distributed under the terms of the Creative Commons
Attribution License (CC BY). The use, distribution or reproduction in other forums
is permitted, provided the original author(s) and the copyright owner(s) are credited
and that the original publication in this journal is cited, in accordance with accepted
academic practice. No use, distribution or reproduction is permitted which does not
comply with these terms.
18 June 2021 | Volume 12 | Article 681876